Nephrol Dial Transplant (1989) 4: 1037-1044
© 1989 European Renal Association-European Dialysis and Transplant Association
research-article
Interstitial Mononuclear Cell Infiltrates in Experimental Nephrosis: Effect of PAF Antagonist
1Department of Pathology, Hospital Ramón y Cajal, Universidad Autónoma-CSIC Madrid, Spain 2Division of Nephrology, Fundación Jiménez Diaz, Universidad Autónoma-CSIC Madird, Spain 3Institut Henri Beafour, Research Laboratories Le Pessis Robinson, France
Correspondence and offprint requests to: Correspondence and offprint requests to: Dr Francisco Mampaso, Dept. Anatomia Patológica, Sección de Immunopatologia, Hospital Ramón y Cajal, Carretera de Colmenar Km 9,100, 28034 Madrid, Spain
Rats receiving a single injection of either aminonucleoside of puromycin (PAN, 10 mg/100 g) or Adriamycin (ADR, 7.5 mg/kg) develop heavy proteinuria and tubulointerstitial nephritis. Interstitial mononuclear cells were markedly more intense in PAN- than in ADR-treated rats. The composition of cell infiltrates was characterised in frozen kidney sections using an immunoperoxidase staining method and a panel of specific monoclonal antibodies. The severe mixed cellular lesions observed in the PAN model on day 14 were dominated by ED1+ macrophages, OX6+ Ia-interstitial and OX8+ T-cytotoxic/suppressor cell surface markers. A similar but more discrete ADR-interstitial cell accumulation was observed on day 11 of the experiment. A correlation existed in the PAN model between the severity of interstitial nephritis and the degree of proteinuria. In contrast, there was no such correlation in ADR nephrosis. Administration of PAF antagonist (BN 52021), started on the first day and continued throughout the 4 weeks of the experiment, induced in both ADR and PAN-treated rats a partial reduction in the number of interstitial cell infiltrates. Glomeruli from normal control rats incubated with 3H acetate, substrate for lyso-PAF: acetyl-CoA acetyltransferase and ADR stimulated PAF generation. Although the precise mechanism of interstitial cell accumulation in these two models of nephrosis are still unknown, our results suggest that PAF could be an important factor involved in interstitial cell recruitment.
Keywords: Cell infiltrates; Nephrosis; PAF; PAF antagonists
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